Requirement of the MASH-1 transcription factor for neuroendocrine differentiation of thyroid C cells.
Thyroid C cells are neural crest-derived neuroendocrine cells that can acquire features similar to serotonergic neurons. Based on developmental and phenotypic markers, we have previously proposed that C cells and serotonergic enteric neurons arise from a common sympathoadrenal progenitor. In this report, we genetically examined this relationship using mice lacking the mammalian achaete-scute homologue 1 (MASH-1) transcription factor, since MASH-1 has recently been shown to be required for differentiation of serotonergic enteric neurons. We found that MASH-1 knockout mice have a greatly reduced number of C cells based on the lack of calcitonin and serotonin immunoreactivity. In contrast, calcitonin and serotonin were still expressed in cultured mature C cells that no longer express MASH-1, demonstrating that MASH-1 is not directly required for the expression of these two markers. Hence, MASH-1 is required to establish the C-cell phenotype and supports the model that C cells lie in the neuronal differentiation pathway of the sympathoadrenal neural crest.
Lanigan
T M
TM
Molecular Biology Program, University of Iowa, Iowa City 52242, USA.
DeRaad
S K
SK
Russo
A F
AF
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002116:Calcitonin / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D009490:Neurosecretory Systems / Q000166:cytology* / Q000196:embryology; D009924:Organ Culture Techniques; D012701:Serotonin / Q000096:biosynthesis; D013194:Staining and Labeling; D013961:Thyroid Gland / Q000166:cytology* / Q000196:embryology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D002116:Calcitonin; D004268:DNA-Binding Proteins; D012701:Serotonin; D014157:Transcription Factors; C499317:Ascl1 protein, mouse